Overexpression of ORMDL3 confers sexual dimorphism in diet-induced non-alcoholic steatohepatitis.

ABSTRACT:

Objective

The bioactive sphingolipid metabolites ceramide and sphingosine-1-phosphate (S1P) accumulate with overnutrition and have been implicated in non-alcoholic steatohepatitis (NASH) development. ORMDL3, a negative regulator of the rate-limiting step in ceramide biosynthesis, has been identified as an obesity-related gene. Therefore, we assessed the role of ORMDL3 in diet-induced obesity and development of NASH.

Methods

Globally overexpressing Ormdl3-Flag transgenic mice (ORMDL3^TG) were fed a western high-fat, carbohydrate and cholesterol enriched diet, with high fructose-glucose drinking water. Physiological, biochemical and sphingolipidomic analyses were employed to measure the effect of ORMDL3 overexpression on NASH development.

Results

ORMDL3^TG

SUBMITTER: Brown RDR 

PROVIDER: S-EPMC10772294 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature